Authors:Niessner A; Agewall S.Pages: 191 - 192Abstract: We would like to congratulate the authors of the COMPASS trial for finishing this well-conducted randomized controlled trial which was one of the largest in the cardiovascular field ever.1 The well-grounded rationale of the study was to reduce frequent major cardiovascular events (MACE) further in patients with stable coronary artery disease (CAD)2 with intensified antithrombotic therapy. The choice of a novel oral anticoagulant (NOAC) for intensification in addition to aspirin is obvious due to the overall beneficial efficacy–safety ratio of these compounds. While using a lower dose of an NOAC may still provide a clinical effect, bleeding may also be elevated.3 Indeed, in the COMPASS trial, the combination of aspirin with rivaroxaban 2.5 mg b.i.d. reduced the primary efficacy endpoint of MACE by 1.3% and increased the primary safety endpoint of major bleeding by 1.2% during a mean follow-up of 23 months. Rivaroxaban alone (5 mg b.i.d.) increased the risk of major bleeding by 0.9% compared with aspirin without improving efficacy. We will critically appraise characteristics of the study with a particular focus on their relevance for implications of the tested therapy in clinical practice.PubDate: Thu, 02 Aug 2018 00:00:00 GMTDOI: 10.1093/ehjcvp/pvy027Issue No:Vol. 4, No. 4 (2018)

Authors:Albani S; Fabris E, Doimo S, et al.Pages: 195 - 201Abstract: AimsThe occurrence of drug intolerance (DI) after an acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI) is an important reason for quitting treatment. Nevertheless, the association between DI and major cardiac and cerebrovascular events (MACCE) is poorly reported in the literature, therefore, we analysed potential relationship between DI and MACCE (a composite of ACS, PCI, heart failure, and stroke) during follow-up.Methods and resultsFrom 1 January 2014 to 31 December 2015, 891 consecutive patients after ACS or coronary revascularization were referred to cardiac rehabilitation (CR) programme and included in a dedicated registry where DI was analysed and treatment appropriately tailored. Three hundred and nine patients (34.7%) developed DI, 26.9% of them were female. Angiotensin-converting enzyme (ACE) inhibitors and statins were the most frequent drugs which caused DI, followed by beta-blockers and calcium channel blockers, in 13.1%, 12.8%, 7.5%, and 5.5% of patients, respectively. During a median follow-up of 18 (interquartile range 11–24) months after CR, MACCE occurred in 14.1% of patients with DI and 8.1% without DI (P = 0.007). At multivariable model, DI to 1 drug [odds ratio (OR) 1.8, 95% confidence interval (CI) 1.01–3.18; P = 0.043] or to 2 drugs (OR 2.56, 95% CI 1.27–5.17; P = 0.008) were independently associated to MACCE. Regarding the association of specific class of prognostic drugs to MACCE, only DI to ACE-inhibitors was independently associated with MACCE (OR 2.31, 95% CI 1.14–4.65; P = 0.019).ConclusionDI was frequently encountered in real-world clinical practice and was significantly associated with MACCE during follow-up. This study suggests that early occurrence of DI could be considered to be an adjunctive cardiovascular risk factor during secondary prevention.PubDate: Tue, 29 May 2018 00:00:00 GMTDOI: 10.1093/ehjcvp/pvy017Issue No:Vol. 4, No. 4 (2018)

Authors:Zeymer U; Cully M, Hochadel M.Pages: 205 - 210Abstract: AimsLittle is known about the adherence to dual antiplatelet therapy with ticagrelor and reasons for discontinuation in real life. Therefore, we evaluated the 12-month course of patients with acute coronary syndromes (ACS) treated with percutaneous coronary intervention (PCI) and ticagrelor during the acute phase.Methods and resultsA total of 614 patients included into the prospective ALKK-PCI Registry between 2014 and 2015 surviving for at least 12 months after discharge provided informations about duration of ticagrelor therapy. In total, 133 patients (21.7%) discontinued ticagrelor prematurely: nine patients before discharge and 124 (20.2%) at a mean 131 days after PCI. Independent baseline predictors for early discontinuation were age >75 years, atrial fibrillation, and prior stroke. Side effects such as dypnoea or bradycardias and bleeding leading to a premature discontinuation of ticagrelor were reported in less than 3% and less than 2% of the total patient population, respectively. In 50% of patients, there was no replacement with another platelet inhibitor after early discontinuation of ticagrelor, while in 28.2% it was replaced by clopidogrel. Bleeding events were observed more often (10.4% vs. 2.7%, P < 0.001) and coronary artery bypass grafting (CABG) (5.3% vs. 0, 4%, P < 0.001) was performed more often in patients with early discontinuation.ConclusionIn this real-life experience of ticagrelor in patients with ACS 22% of patients discontinued ticagrelor early. Side effects were the cause for discontinuation in only 3%, while age >75 years, prior stroke, atrial fibrillation, CABG, and bleeding during follow-up were associated with premature discontinuation.PubDate: Thu, 07 Jun 2018 00:00:00 GMTDOI: 10.1093/ehjcvp/pvy018Issue No:Vol. 4, No. 4 (2018)

Authors:Raatikainen M; Penttilä T, Korhonen P, et al.Pages: 211 - 219Abstract: AimsThe impact of the quality of warfarin therapy on cardiovascular outcomes excluding stroke is largely unknown. The aims of this study were to evaluate the association between the warfarin control and the incidence and outcome of myocardial infarction (MI) and to validate the predictive value of the CHA2DS2-VASc score for MI in atrial fibrillation (AF) patients taking warfarin.Methods and resultsThe nationwide FinWAF Registry consists of 54 568 AF patients (mean age 73.31 ± 10.7 years, 52% men) taking warfarin. The quality of warfarin therapy was assessed continuously by calculating the time in therapeutic range within a 60-day window using the Rosendaal method (TTR60). Adjusted Cox proportional hazards models were prepared for the incidence of MI and cardiovascular mortality in six different TTR60 categories. During the 3.2 ± 1.6 years of follow-up, the annual incidence of MI (95% confidence interval) was 3.3% (3.0–3.5%), 2.9% (2.6–3.3%), 2.4% (2.1–2.7%), 1.9% (1.7–2.2%), 1.7% (1.5–2.0%), and 1.2% (1.1–1.3%) among patients with TTR60 <40%, 40–50%, 50–60%, 60–70%, 70–80%, and >80%, respectively. Well-managed warfarin therapy (TTR60 > 80%) was associated also with a lower cardiovascular mortality, whereas a high CHA2DS2-VASc score correlated with poor outcome.ConclusionCardiovascular outcome was superior among AF patients with good warfarin control and in those with a low CHA2DS2-VASc score. The inverse association between the TTR60 and incidence of MI and cardiovascular mortality indicate that in AF patients the quality of warfarin therapy is critical not only for prevention of stroke but also with regard to cardiovascular outcome.PubDate: Mon, 05 Mar 2018 00:00:00 GMTDOI: 10.1093/ehjcvp/pvy009Issue No:Vol. 4, No. 4 (2018)

Authors:Sindet-Pedersen C; Staerk L, Pallisgaard J, et al.Pages: 220 - 227Abstract: AimsTo investigate the risk of all-cause mortality, recurrent venous thromboembolism (VTE), and hospitalized bleeding in patients with VTE treated with either rivaroxaban or apixaban.Methods and resultsUsing Danish nationwide registries, patients with VTE treated with rivaroxaban or apixaban in the period from 1 January 2015 to 30 June 2017 were identified. Standardized absolute risks were estimated based on outcome-specific Cox regression models, adjusted for potential confounders. A total of 8187 patients were included in the study, of which 1504 (18%) were treated with apixaban [50% males, median age 70 years; interquartile range (IQR) 56–80] and 6683 (82%) were treated with rivaroxaban (55% males, median age 67 years; IQR 53–76). The 180 days risk of all-cause mortality was 5.08% [95% confidence interval (95% CI) 4.08% to 6.08%)] in the apixaban group and 4.60% (95% CI 4.13% to 5.18%) in the rivaroxaban group [absolute risk difference: −0.48% (95% CI −1.49% to 0.72%)]. The 180 days risk of recurrent VTE was 2.16% (95% CI 1.49% to 2.88%) in the apixaban group and 2.22% (95% CI 1.89% to 2.52%) in the rivaroxaban group [absolute risk difference of 0.06% (95% CI −0.72% to 0.79%)]. The 180 days risk of hospitalized bleeding was 1.73% (95% CI 1.22% to 2.35%) for patients in the apixaban group and 1.89% (95% CI 1.56% to 2.20%) in the rivaroxaban group [absolute risk difference: 0.16% (95% CI −0.59% to 0.81%)].ConclusionIn a nationwide cohort of 8187 patients with VTE treated with rivaroxaban or apixaban, there were no significant differences in the risks of all-cause mortality, recurrent VTE, or hospitalized bleeding.PubDate: Tue, 26 Jun 2018 00:00:00 GMTDOI: 10.1093/ehjcvp/pvy021Issue No:Vol. 4, No. 4 (2018)

Authors:Vonbank A; Drexel H, Agewall S, et al.Pages: 230 - 236Abstract: With statins, the reported rate of adverse events differs widely between randomized clinical trials (RCTs) and observations in clinical practice, the rates being 1–2% in RCTs vs. 10–20% in the so-called real world. One possible explanation is the claim that RCTs mostly use a run-in period with a statin. This would exclude intolerant patients from remaining in the trial and therefore favour a bias towards lower rates of intolerance. We here review data from RCTs with more than 1000 participants with and without a run-in period, which were included in the Cholesterol Treatment Trialists Collaboration. Two major conclusions arise: (i) the majority of RCTs did not have a test dose of a statin in the run-in phase. (ii) A test dose in the run-in phase was not associated with a significantly improved adherence rate within that trial when compared to trials without a test dose. Taken together, the RCTs of statins reviewed here do not suggest a bias towards an artificially higher adherence rate because of a run-in period with a test dose of the statin. Other possible explanations for the apparent disparity between RCTs and real-world observations are also included in this review albeit mostly not supported by scientific data.PubDate: Tue, 07 Aug 2018 00:00:00 GMTDOI: 10.1093/ehjcvp/pvy028Issue No:Vol. 4, No. 4 (2018)

Authors:Hallén J; Sreeharan N.Pages: 237 - 242Abstract: The prevalence of hypertriglyceridaemia is high and growing in several parts of the world. Hypertriglyceridaemia has a well-defined association with the risk of atherosclerotic cardiovascular (CV) disease and triglycerides represent a potential target for drugs aimed at mitigating CV risk. So far, no triglyceride-lowering pharmacological strategy has succeeded in conclusively showing the ability to modify clinical outcomes. This article discusses strategic and clinical aspects of development of triglyceride-lowering drugs to address CV disease.PubDate: Fri, 27 Jul 2018 00:00:00 GMTDOI: 10.1093/ehjcvp/pvy029Issue No:Vol. 4, No. 4 (2018)